This paper describes the inner workings of centrioles (a pair of small organelles adjacent to the nucleus) as they create cell electropolarity, engage in cell division (mitosis), but in going awry, also promote the development of cancers. The electropolarity arises from vibrations of microtubules composing the centrioles. Mitosis begins as each centrioles duplicates itself by growing a daughter centriole on its side. If during duplication more than one daughter is grown, cancer can occur and the cells divide uncontrollably. Cancer cells with supernumerary centrioles have high electropolarity which can serve as an attractor for charged therapeutic nanoparticles.

Centrioles are tiny organelles lying adjacent to the nucleus of human and animal (eukaryotic) cells (see Fig. 1). Although their existence has been known for now over 100 years [1-7], centrioles have only recently been studied in any significant detail. This recent interest has been stimulated by: (1) dramatic advances in imaging technologies resulting in a better understanding of centriole geometry; (2) improved understanding of the important role of centrioles in cell mechanics—particularly in mitosis; and (3) the increasing belief that centriole malfunction occurs in virtually all solid tumor cancers.

It is now known that centrioles have the following properties:

(1)They have precise geometry, occurring in pairs as small annular cylinders (approximately 400 nm of long and 200 nm in diameter), with cylinder axes perpendicular to one another.

(2)As with deoxyribonucleic acid (DNA) centrioles are self-duplicating and they duplicate at approximately the same time as DNA duplicates.

(3)Centrioles are the only organelles without a membrane cover.

(4)Centrioles are active participants in the cell division (mitosis) process.

(5)During the S-phase of normal cell mitosis, each centriole duplicates once and only once. In abnormal mitosis, centrioles may duplicate multiple times and with disrupted geometry.

Interestingly, approximately 45 years ago, Dr. Paul Schafer, while working at the Veterans Administration Hospital in Washington, D.C., discovered and reported [8-10] that esophageal cancer cells have distorted centriole geometries. He suggested that cancers develop due to abnormalities in the electromagnetic fields surrounding the centrioles.

Unfortunately, as with Boveri, Schafer's work has received relatively little attention until recently.

The following paragraphs summarize recent and state-of-the-art findings about centrioles, their inner workings, and their overall effect upon cell electropolarity. How these findings could be an aid in cell research is also discussed—particularly in solving the problem of in vivo insertion of therapeutic nanoparticles [11].

Figure 1 provides a typical drawing of a cell interior. The centrioles are seen as the small perpendicular organelles adjacent to the nucleus. In Fig. 2, we have a closer view of the centriole pair.

Each centriole cylinder consists of nine “blades” of microtubules (MTs). Each blade in turn has three MTs with slightly different lengths, with the longest being on the interior of the blade and the shortest to the outside, as in Fig. 3 [12,13].

Taken together, the centriole cylinder consists of 27 parallel MTs arranged symmetrically about the central axis. The center of the centriole, called the “lumen” is composed of the γ-tubulin protein.

An MT is itself a hollow cylindrical structure consisting of 13 parallel tubulin filaments, or strands, composed of alternating α- and β-tubulin proteins. The outside diameter of an MT cylinder is approximately 25 nm. The inside diameter is approximately 16 nm. The MT length varies as tubulin is added at the base, in the centriole it remains at about 400 to 500 nm [12,14,15].

With centrioles consisting primarily of MTs, the centriole cylinder length is thus also 400 to 500 nm. The cylinder diameter is approximately 200 nm [12,13,16].

As noted, centrioles occur in pairs, but in that pair, one is older, or more mature, and known as the “mother.” The other centriole (the “daughter”) is less well developed and only about 80% as long as the mother. The daughter centriole is attached to the base, or proximal, end of the mother centriole [17,18]. In this configuration, the axis of the daughter intersects the axis of the mother, with the axes of the two centrioles being perpendicular.

Surrounding the centriole pair, at the adjoining base, is an amorphous cloud of numerous proteins known as the MT organizing center (MTOC) [13,19]. The centrioles together with the MTOC are known as the centrosome. The centrosome, being roughly spherical, has a diameter of approximately 4 μm.

The MTOC is believed to be “electron dense” [3,13]. In this regard, with the MTOC at the intersecting bases of the centriole pair, the proximal or base end of the centriole is given negative polarity or potential. The distal ends are thus positive.

Centrioles are the principal drivers of cell division and duplication (mitosis). Mitosis is typically described as occurring in four phases: In the first phase (the “prophase”), each centriole becomes a new “mother” centriole supporting the creation of a new daughter centriole on its side and at its proximal end. As these daughter centrioles develop and grow, the original centriole pair becomes two pair, with the original mother centriole having a new daughter, and the original daughter having a new daughter of its own [12,13,20-23].

During the time that the centrioles are duplicating, the nucleus membrane begins to soften, break down, and the DNA condenses in preparation for division.

Finally, the connection between the centriole pairs stretches and the pairs move apart. Interestingly, the original mother centriole with its new daughter remains somewhat stationary while the less mature daughter-new daughter centriole pair moves away, around the nucleus to the opposite side. During the movement, this immature centriole pair becomes mature. Even though the centriole pairs are separating, they remain connected by MTs about the collapsing nucleus—almost in the shape of a football. Taken as a group, these MTs are known as the “mitotic spindle” (see Fig. 6).

The remaining three phases (metaphase, anaphase, and teleophase) complete the cell separation process with the metaphase being the creation of a symmetric structure between the two pairs of centrioles; the anaphase being the separation in the midplane; and finally, the teleophase being the formation of new nuclear membranes about the separated parts.

The two centriole pairs each align themselves adjacent to the separated nuclei respectively. The separated nuclii then move further apart, each taking with it approximately half of the original cell organelles and half of the remaining cell material (the cytoplasm). Thus the original cell becomes two cells [12,20].

Numerous studies [24-31] have shown that the MTs within a centriole generate an electromagnetic field about the centriole. This field is believed to occur due to longitudinal (axial) vibration of the MT filaments.

Consider again Fig. 3 showing again a sketch of an MT, (1 of 27), parallel to the axis of the centriole barrel. The proximal (or base) end of the MT is immersed in the electron dense material of the MTOC [3,13,32,33]. With this proximal end being negative, and thus the distal end being positive, this positive distal end is immersed in the cloud of material of the centrosome, or pericentriolar material.

As noted earlier, the MT filaments are composed of alternate α-tubulin and β-tubulin protein pairs (“dimers”). A single dimer has a high electric charge difference (polarity) along its axis. Then with the filament dimers being arranged in a series of dimers along the filament length, there is a voltage change from the proximal (negative) to the distal (positive) end of the filament [24-29]. It is the tubulin that is the source of this potential difference [27].

An MT filament surface is relatively smooth, allowing for relatively free longitudinal, oscillatory movement (vibration) of the filament. Then taken together the longitudinal, or axial, vibration of the 13 filaments of an MT and then the 27 MTs making up the centriole barrel produce the electromagnetic field surrounding the centriole [25,29,34,35]. Interestingly, this field is also found to be ferromagnetic [36-39].

Also of interest, the fundamental vibration frequency of an MT filament is approximately 465 MHz [40], although this frequency is continually changing due to the ongoing length changing of the filaments.

The electropolarity of the centrioles enables them to exert forces at a distance—that is, forces without physical contact. Also, it is this high electropolarity of the centriole, lying next to the nucleus, which produces the overall electropolarity of the cell [41]. The transepithelial potentials, that is, the potential difference across a cell membrane cover may range from a few millivolts to tens of millivolts.

Finally, as one would expect, the peak of cell electropolarity occurs during mitosis [25], when there are four, instead of two, centrioles. Correspondingly, the MTs then orient the mitotic spindle along the axis of cell polarity [42].

From a physical perspective, cancer cells are softer than normal, or healthy cells [50]. Then being less stiff, cancer cells have lower fundamental vibration frequencies than noncancerous cells. Also, cancer cells appear to have greater damping of electromagnetic waves than normal cells [29]. But perhaps of greatest interest from a physical perspective is that cancer cells have an enhanced electromagnetic field and with negative electropolarity [51-53]. This enhanced negative polarity is consistent with the presence of supernumerary centriole cells and of cells with centrosome amplification. Indeed, some breast cancer tumors reportedly have sufficiently enhanced potential that they can be detected in vivo over the breast surface [54].

The supernumerary centrioles and corresponding centrosome amplification give rise to rapid cell division and uncontrolled growth—the characteristic of cancer cells. A question arising is: Are cells cancerous due to the presence of centrosome amplification, or is it disrupted centriole geometry which makes a cell cancerous? The current thinking of analysts is that cancerous cells do in fact have centrosome amplification and centriole clustering, but that the origin of the amplification and clustering is a single centriole defect [3,31,44,46,47,55-65].

What then causes the defect? There appear to be many causes ranging from possible protein excesses (e.g., Plk4), possible protein deficiencies (e.g., P53), radiation exposure, electromagnetic exposure, and excessive exposure to carcinogens. Of these, P53 deficiencies have attracted attention of researchers since P53 is believed to be a regulator of centrosome duplication and a tumor suppressor [2,13,46,59,66-69]. These many causes of centriole defects are beyond the scope of this paper. Nevertheless, a commonly occurring initial centriole defect is the growth of two or more daughter centrioles at the base of the mother centriole—as flower petals [47] (see Fig. 7).

The references provide additional information about the foregoing findings and observations. Not surprisingly, as revealing as these findings are, they also raise questions and an interest in obtaining additional details. To this end, the following paragraphs provide a summary of the principal findings and a listing of needs for additional studies, and for additional experimental data.

Findings

(1)Electromagnetics play an important role in cell functioning and especially in cell duplication and division (mitosis).

(2)Cell electropolarity arises from the centrioles via the MTs of the centriole blades.

(3)The MTs obtain their polarity via α, β dimers arranged in series along the filaments of the MT wall.

(4)Overall cell electropolarity is increased during mitosis due to the presence of two pairs of centrioles.

(5)Overall cell electropolarity is even greater in cancer cells due to the presence of supernumerary centrioles and centriole clustering. Indeed, supernumerary centrioles tend to cluster together—apparently due to electromagnetic attraction [70].

(6)Clinically, it is found that breast cancer tissue has sufficiently large electrical polarity that it can be detected relative to surrounding tissue at the breast surface [54], and the aggressiveness of breast cancer is proportional to the degree of centrosome amplification.

(7)In general, there is a small but steady extracellular voltage gradient between cancer tissue and neighboring normal tissue [71-73].

(8)Centrosomal amplification is regarded as a “hallmark” of cancer cells [74,75]—that is, all major cancer cells have centrosomal amplification [59,67,76,77].

(9)In an early stage of mitosis, electromagnetic forces send the less mature pair of centrioles around the nucleus to the other side.

(10)The electropolarity associated with centriole clustering may be useful for tumor identification and treatment using charged nanoparticles.

Open Questions and Needed Data

(1)Why is centriole geometry so precise and why does it have the particular form that it has?

(2)During centriole duplication, why does the daughter centriole arise and develop on the side and at the base of the mother centriole?

(3)What is the magnitude of the electropolarity change along a centriole length, across a centriole pair, and across a duplicating pair of centrioles?

(4)What is the magnitude of the electropolarity change across a centriole cluster of a cancer cell?

(5)Is the electropolarity of a centriole cluster sufficiently strong to attract charged nanoparticles?

(6)What is the range of frequencies of the longitudinal vibrations of MTs with variable lengths?

(7)What is the three-dimensional map of potential of a normal cell?

Additional experimentation will be required to answer these questions. To this end, it now appears that the best approach is to use current nanotechnology including the use of atomic force microscopy with magnetic sensitive probing tips. This is a subject of ongoing local research.

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